Coronary angioplasty is an intravascular surgery for dilating an occluded or stenosed lesion in the artery of the heart (coronary artery) by applying the catheterization. It is used for the therapy of ischemic heart diseases such as angina pectoris or myocardial infarction. Coronary angioplasty is called percutaneous transluminal coronary angioplasty (hereinafter abbreviated as PTCA) or percutaneous coronary intervention (hereinafter abbreviated as PCI) (hereinafter, the term “PTCA” is used in the present invention to include both PTCA and PCI.). Examples of the type of an apparatus used in the angioplasty may include a balloon (balloon catheter), reticulated metal (stent), a rapidly rotating olive-shaped drill (rotor plate), and DCA in which a cutter is pressed against arteriosclerotic tissues to incise them. Since PTCA is a treatment which mechanically dilates blood vessels, a fetal complication may be occasionally developed. Other than such a complication, “restenosis”, wherein the dilated portion is narrowed again, is also problematic. It has been reported so far that various types of antioxidant substances suppress neointimal formation in animal models injured by use of a balloon (Gordon A. A., et al., Proc. Natl. Acad. Sci., USA, 89, 11312-11316, 1992).
Regarding a pyrazolone derivative which is represented by the following formula (I):
wherein R1 represents a hydrogen atom, aryl, C1-5 alkyl, or C3-6 (total carbon number) alkoxycarbonylalkyl, R2 represents a hydrogen atom, aryloxy, arylmercapto, C1-5 alkyl or C1-3 hydroxyalkyl, or R1 and R2 are combined with each other to represent C3-5 alkylene group, and R3 represents a hydrogen atom, C1-5 alkyl, C5-7 cycloalkyl, C1-3 hydroxyalkyl, benzyl, naphthyl or phenyl, or phenyl substituted with the same or different 1 to 3 substituents selected from the group consisting of C1-5 alkoxy, C1-3 hydroxyalkyl, C2-5 (total carbon number) alkoxycarbonyl, C1-3 alkylmercapto, C1-4 alkylamino, C2-8 (total carbon number) dialkylamino, halogen atom, trifluoromethyl, carboxyl, cyano, hydroxyl group, nitro, amino and acetamide), examples of the known medical applications include cerebral function-normalizing action (JP Patent Publication (Kokoku) No. 5-31523 B (1993)), lipid peroxide production-suppressing action (JP Patent Publication (Kokoku) No. 5-35128, B (1993), antiulcer action (JP Patent Publication (Kokai) No. 3-215425 (1991)) and anti-hyperglycemic action (JP Patent Publication (Kokai) No. 3-215426 (1991)).
Among the compounds represented by the above formula (I), a pharmaceutical preparation containing 3-methyl-1-phenyl-2-pyrazolin-5-one as an active ingredient has been commercially available as a protective agent for the brain (under the general name “edaravone” and the commercial name “Radicut”: produced and marketed by Mitsubishi Pharma Corporation) since June 2001. This “edaravone” has been reported to have high reactivity to active oxygen (Kawai, H., et al., J. Phamacol. Exp. Ther., 281(2), 921, 1997; and Wu, T W. et al., Life Sci, 67(19), 2387, 2000). As described above, edaravone is a free radical scavenger which prevents cell damage and the like by removing various free radicals including active oxygen. However, a study of whether or not edaravone is effective against arterial wall injury, has not been reported at all.